Inhibition of cancer cell invasion by new ((3,4-dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide analogs

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• 作者：Seong-Mook Kang^a ; Ky-Youb Nam^b ; Seung-Youn Jung^a ; Kyung-Hee Song^a ; Seongho Kho^a ; Kyoung Tai No^c ; Hyun Kyung Choi^d ; ^&dagger ; ; ^{hkchoi45@jwu.ac.kr" class="auth_mail" title="E-mail the corresponding author} ; Jie-Young Song^a ; ^&dagger ; ; ^{immu@kirams.re.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：((3 ; 4-Dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide ; Protein&ndash ; protein blocker ; Rab27a ; Rab GTPases ; Intracellular membrane trafficking ; Invasion ; Metastasis
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 February 2016
• 年：2016
• 卷：26
• 期：4
• 页码：1322-1328
• 全文大小：4114 K

文摘

Rab GTPases regulate various types of intracellular membrane trafficking in all eukaryotes. Since Rab27a and its multiple effectors are involved in exocytosis of lysosome-related organelles and play a major role in malignancy, compounds targeting Rab27a could be likely used to inhibit invasive growth and tumor metastasis. Thus, we designed and synthesized several compounds based on the previously reported Rab27a-targeting synthetic compounds identified by virtual screening, and investigated their anti-metastatic effects in MDA-MB231 and A375 cells. Among the synthesized compounds, (E)-N-(3-chlorophenyl)-6-(2-(3,4-dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide (3d) and (E)-N-benzyl-6-(2-(3,4-dihydroxy benzylidene)hydrazinyl)-N-methylpyridine-3-sulfonamide (3f) significantly inhibited the invasiveness of both tumor cell lines. Compounds 3d and 3f also decreased the levels of signature extracellular matrix marker proteins (fibronectin, collagen, and α-smooth muscle actin) and representative mesenchymal cell markers (N-cadherin and vimentin). Taken together, our results suggest that novel sulfonamide analogs have anti-metastatic activity in breast and melanoma cancer cell lines and may be used as therapeutic agents to treat malignant cancer.